Lithium (Li) salts are often used in treating affective disorders. But even at adequate serum concentrations, nearly 30% of the patients do not respond to Li treatment. There is a strong possibility that this subgroup of patients does not generate adequate brain lithium concentrations. Thus a true measure of brain Li concentration may be the key factor in effective treatment of nonresponders. Those patients who are resistant to lI treatment alone often show considerable improvement with the addition of carbamazepine (anti-convulsant and an alternative to lithium). Localized (7) Li spectroscopic studies in rat brain will be conducted in an effort to understand the effect of psychopharmacological agents on Li in the mammalian brain. Preliminary studies on rat brain via localized (7) Li spectroscopy have demonstrated the feasibility of this technique for studying both the dose response and the pharmacokinetics in a quantitative fashion. The rat brain will be studied with the following specific aims; 1) using the Stimulated Echo Acquisition Mode (STEAM) spectroscopy, obtain localized (7) Li T1, T2, and NMR visibility data necessary for the rest of these studies, 2) measure the effect of a representative psychopharmacological agent such as carbamazepine on Li dose response and pharmacokinetics, 3) perform in vitro atomic absorption studies on the rat brain in support of in vivo studies, and 4) perform behavioral toxicity experiments on rats to correlate with the serum and brain Li levels. A comparative study of the effects of carbamazepine and of no added drug on brain Li relaxation times, dose-tissue concentration, and pharmacokinetics will be conducted. The long-term objective of this proposal is to apply similar techniques to human patients, studying both those on Li alone and those on Li plus an added psychopharmacological agent. The ultimate goal is to obtain sufficient knowledge of th interaction of Li and coadministered drugs to help clinicians design improved treatment regimens.